Diagnostic Delay of Celiac Disease in Childhood.

Importance: The extent and factors associated with risk of diagnostic delay in pediatric celiac disease (CD) are poorly understood. Objectives: To investigate the diagnostic delay of CD in childhood, and to assess factors associated with this delay. Design, Setting, and Participants: Multicenter, retrospective, cross-sectional study (2010-2019) of pediatric (aged 0-18 years) patients with CD from 13 pediatric tertiary referral centers in Italy. Data were analyzed from January to June 2023. Main Outcomes and Measures: The overall diagnostic delay (ie, the time lapse occurring from the first symptoms or clinical data indicative of CD and the definitive diagnosis), further split into preconsultation and postconsultation diagnostic delay, were described. Univariable and multivariable linear regression models for factors associated with diagnostic delay were fitted. Factors associated with extreme diagnostic delay (ie, 1.5 × 75th percentile) and misdiagnosis were assessed. Results: A total of 3171 patients with CD were included. The mean (SD) age was 6.2 (3.9) years; 2010 patients (63.4%) were female; and 10 patients (0.3%) were Asian, 41 (1.3%) were Northern African, and 3115 (98.3%) were White. The median (IQR) overall diagnostic delay was 5 (2-11) months, and preconsultation and postconsultation diagnostic delay were 2 (0-6) months and 1 (0-3) month, respectively. The median (IQR) extreme overall diagnostic delay (586 cases [18.5%]) was 11 (5-131) months, and the preconsultation and postconsultation delays were 6 (2-120) and 3 (1-131) months, respectively. Patients who had a first diagnosis when aged less than 3 years (650 patients [20.5%]) showed a shorter diagnostic delay, both overall (median [IQR], 4 [1-7] months for patients aged less than 3 years vs 5 [2-12] months for others) and postconsultation (median [IQR], 1 [0-2] month for patients aged less than 3 years vs 2 [0-4] months for others). A shorter delay was registered in male patients, both overall (median [IQR], 4 [1-10] months for male patients vs 5 [2-12] months for female patients) and preconsultation (median [IQR], 1 [0-6] month for male patients vs 2 [0-6] months for female patients). Family history of CD was associated with lower preconsultation delay (odds ratio [OR], 0.59; 95% CI, 0.47-0.74) and lower overall extreme diagnostic delay (OR, 0.75; 95% CI, 0.56-0.99). Neurological symptoms (78 patients [21.5%]; OR, 1.35; 95% CI, 1.03-1.78), gastroesophageal reflux (9 patients [28.1%]; OR, 1.87; 95% CI, 1.02-3.42), and failure to thrive (215 patients [22.6%]; OR, 1.62; 95% CI, 1.31-2.00) showed a more frequent extreme diagnostic delay. A previous misdiagnosis (124 patients [4.0%]) was more frequently associated with gastroesophageal reflux disease, diarrhea, bloating, abdominal pain, constipation, fatigue, osteopenia, and villous atrophy (Marsh 3 classification). Conclusions and Relevance: In this cross-sectional study of pediatric CD, the diagnostic delay was rather short. Some factors associated with risk for longer diagnostic delay and misdiagnosis emerged, and these should be addressed in future studies.

Effectiveness of Preoperative Immunonutrition in Improving Surgical Outcomes after Radical Cystectomy for Bladder Cancer: Study Protocol for a Multicentre, Open-Label, Randomised Trial (INu-RC).

Radical cystectomy (RC) with pelvic lymph node dissection is the standard treatment for patients with limited-stage muscle-invasive bladder cancer. RC is associated with a complication rate of approximately 50-88%. Immunonutrition (IMN) refers to the administration of substrates, such as omega-3 fatty acids, arginine, glutamine, and nucleotides, that modulate the immune response. IMN has been associated with improved outcomes following surgery for esophagogastric, colorectal and pancreatic cancer. In this paper, we describe a study protocol for a multicentre, randomised, open-label clinical trial to evaluate the effect of IMN in patients undergoing RC for bladder cancer. A 7-day preoperative course of IMN is compared with a standard high-calorie high-protein oral nutritional supplement. The primary outcome of this study is the rate of complications (infectious, wound-related, gastrointestinal, and urinary complications) in the first 30 days after RC. Secondary outcomes include time to recovery of bowel function and postoperative mobilisation, changes in muscle strength and body weight, biochemical modifications, need for blood transfusion, length of stay, readmission rate, and mortality. The results of this study may provide new insights into the impact of IMN on postoperative outcomes after RC and may help improve IMN prescribing based on patient nutritional status parameters.

A Longitudinal RCT on the Effectiveness of a Psychological Intervention for Hospital Healthcare Workers During the COVID-19 Pandemic: What We Learned to Date.

The COVID-19 pandemic has led to significant psychological distress among frontline healthcare workers (HCWs), with a particular increase in trauma-related symptoms. This study investigated the longitudinal course of trauma-associated symptoms and behaviors in HCWs and the effectiveness of a brief dialectical behavior therapy (DBT)-informed intervention in mitigating these symptoms over 12 months. The trial included 225 HCWs randomly assigned to one of three groups: no intervention (control), in-person DBT-informed intervention, or online DBT-informed intervention. Over time, a natural decrease in PTSD symptoms was observed in all groups. Contrary to expectations, no difference was found between the control and intervention groups. However, for participants with severe PTSD symptoms, the intervention significantly mitigated their distress. No differences emerged between in-person and online interventions, suggesting equal effectiveness. Females reported higher trauma-related symptoms, while no differences emerged among different professional roles. These findings underscore the importance of targeted interventions for HCWs experiencing severe symptoms and highlight the potential of online modalities. Further research is needed to optimize the deployment of mental health resources within the healthcare setting, particularly during crises.

Long-Term Natural History of Autoimmune Gastritis: Results From a Prospective Monocentric Series.

INTRODUCTION: The natural history of autoimmune gastritis (AIG) has been poorly described. In this study, we report the long-term natural history and clinical clustering of the full spectrum of AIG, from the potential to the complicated stage. METHODS: Prospective single-center study conducted in a tertiary referral center. Patients with AIG at any stage (0 = potential; 1 = early; 2 = florid; 3 = severe; and 4 = complicated) were enrolled (January 2000-December 2022). The histopathological evolution, the clinical presentation, and the correlates of evolution of potential AIG were assessed. RESULTS: Four hundred ninety-eight patients with AIG (mean age 56.7 ± 15.2 years, F:M ratio 2.5:1) were included, of whom 93 experienced potential AIG. The maximum disease duration was 27 years (median 18, interquartile range 14-23), while the overall median follow-up was 52 months (interquartile range 12-95). Age was significantly lower in stage 0 compared with that in the other stages. Accidental histologic evidence and hematologic findings were the most common clusters of diagnosis. The overall median rate of progression was 7.29 per 100 persons/yr (95% confidence interval [CI] 6.19-8.59), while the stage-specific rates of progression were 10.85 (stage 0; 95% CI 7.75-15.18), 14.83 (stages 1-2; 95% CI 11.89-18.49), and 2.68 (stage 3; 95% CI 1.88-3.84). Newly onset neoplastic complications at follow-up occurred in 41/483 patients (8.5%; 23 neuroendocrine tumors and 18 epithelial dysplasia). No cases of adenocarcinoma were noticed. Male sex was associated with a greater likelihood of evolving from potential AIG to overt AIG. DISCUSSION: AIG is a progressive disorder, with a virtually absent risk of gastric adenocarcinoma. Patients with potential AIG should be monitored because they carry a high risk of evolving into overt AIG.

Correlation between visual field index and quality of life in glaucoma patients: a new tool to screen quality of life perception?

Purpose: To evaluate the correlation between the visual field index (VFI) and vision-related quality of life (QoL) considering several confounding variables that may have a positive or negative effect. Methods: We conducted a cross-sectional, mono-centric study on glaucoma patients. Quality of life was examined with the NEI-VFQ 25 and the Glaucoma Symptom Scale (GSS). The visual field was examined with the Humphrey Field Analyzer. The variables considered were age, gender, comorbidities, years (at diagnosis and duration of the illness), treatment and related active principles, intraocular pressure, and visual acuity. The analysis was performed on both the better and the worse eye. The linear regression univariate analysis and the multivariate analyses were performed. Results: In total, 193 patients enrolled in the study. The mean age was 70.8 ± 10.4 years. The mean follow-up period since diagnosis 11.4 ± 9.2 years. Approximately 50% of the patients suffered from primary open angle glaucoma (POAG) and 45% were on monotherapy. The mean VFI was 81.3 ± 26. Regarding QoL, the NEI-VFQ total mean was 80.4 ± 17.8 and the GSS total score was 77.2 ± 21. Regarding NEI-VFQ 25, the single linear regression analysis found the following relations: age at time of visit (r = -0.30, p = 0.016), years of illness (r = -0.32, p = 0.020), the minimum and maximal visual acuity (r = 2.04 and r = 3.96, p < 0.001), the IOP min (r = 1.13, p = 0.002) and max (r = -0.52, p = 0.017), and the number of previous surgeries (r = -3.94, p < 0.001). The multivariate analysis found the following relations: gender (r = 5.13, p = 0.019), visual acuity max (r = 3.16, p < 0.001), and previous surgeries (r = -1.80, p = 0.032). Regarding GSS, the single linear regression analysis found relations with visual acuity (r = 2.37, p < 0.001), VFI (r = 0.41, p < 0.001), previous surgeries in the eye considered (r = -7.27, p < 0.001), and number of instillations (r = -3.67, p = 0.031). Data confirmed that a higher VFI has a positive impact on the score of both the NEI-VFQ 25 (r = 0.22, p = < 0.001) and the GSS questionnaire (r = 0.36, p < 0.001). Conclusions: The study demonstrated a correlation between the VFI and QoL of patients and their visual and non-visual ocular symptoms and function both in the worst and in the better eye, even when accounting for several clinical and demographic confounding variables. Our data support that the visual field index is an important metric instrument in the follow up of patients with glaucoma.

Impact of proton pump inhibitors on the onset of gastrointestinal immune-related adverse events during immunotherapy.

INTRODUCTION: The gut microbiota (GM) can influence the pathogenesis of immune-mediated adverse events (irAEs). Proton pump inhibitors (PPIs) can affect the integrity of GM, but their role in promoting irAEs is still poorly understood. METHODS: In this retrospective single-center cohort study, the primary endpoint was the evaluation of the incidence of gastrointestinal (GI) irAEs in cancer patients on PPIs (exposed) versus cancer patients who were not on PPIs (unexposed). RESULTS: Three hundred and sixty three patients' records (248 M/115F, median age 69) were reviewed. Twenty-three exposed patients (92%) developed GI irAEs while only two unexposed patients (8%) developed GI irAEs (hazard ratio [HR] 13.22, 95% confidence interval [CI] 3.11-56.10, p < 0.000). This HR was confirmed after weighting for the propensity score (HR15.13 95% CI 3.22-71.03, p < 0.000). CONCLUSION: Chronic PPI use is associated with an increased risk of GI irAES.

Pharmacokinetics of Venetoclax Co-Administered with Posaconazole in Patients with Acute Myeloid Leukemia.

The Food and Drug Administration currently approves the combination of hypomethylating agents (HMA), azacytidine or decitabine with venetoclax (VEN) for acute myeloid leukemia (AML) patients aged more than 75 years and for patients unsuitable for intensive chemotherapy. The risk of fungal infection in the early phase of treatment is not negligible; therefore, posaconazole (PCZ) is commonly administered as primary prophylaxis. A drug-drug interaction between VEN and PCZ is well known, but the trend of serum levels of venetoclax when both drugs are overlapped is not clear. In total, 165 plasma samples from 11 elderly AML patients receiving combined treatment with HMA, VEN and PCZ were analyzed by a validated analytical method (high-pressure liquid chromatography-tandem mass spectrometry). Venetoclax trough plasma concentrations were detected during the 3 days of ramp-up as well as on day 7 and day 12 of treatment when the exposure as the area under the plasma concentration-time curve and the accumulation ratio were also calculated. The results were compared with the expected data for 400 mg/dose VEN administered alone-the confirmed high inter-individual variability in pharmacokinetics suggests the need for therapeutic drug monitoring.

Impact of SARS-CoV-2 infection in patients with hereditary hemorrhagic telangiectasia: epidemiological and clinical data from the comprehensive Italian retrospective multicenter study.

Rare Disease patients manifested high concern regarding the possible increased risk of severe outcomes and worsening of disease-specific clinical manifestation due to the impact of COVID-19. Our aim was to assess the prevalence, outcomes, and impact of COVID-19 in patients with a rare disease such as Hereditary Hemorrhagic Telangiectasia (HHT) in Italian population. A nationwide, multicentric, cross-sectional observational study was conducted on patients with HHT from five Italian HHT centers by online survey. The association between COVID-19-related signs and symptoms and nosebleeds worsening, the impact of personal protective equipment on nosebleeds pattern, and the relationship between the presence of visceral AVMs and severe outcomes were analyzed. Out of 605 total survey responses and eligible for analysis, 107 cases of COVID-19 were reported. A mild-course COVID-19 disease, not requiring hospitalization, was observed in 90.7% of patients, while the remaining eight cases needed hospitalization, two of them requiring intensive-care access. No fatal outcome was recorded and 79.3% of patients reported a complete recovery. No difference in infection risk and outcome between HHT patients and general population was evidenced. No significative interference of COVID-19 on HHT-related bleeding was found. The majority of patients received COVID-19 vaccination, with relevant impact on symptoms and need for hospitalization in case of infection. COVID-19 in HHT patients had an infection profile similar to the general population. COVID-19 course and outcome were independent from any specific HHT-related clinical features. Moreover, COVID-19 and anti-SARS-CoV-2 measures did not seem to affect significantly HHT-related bleeding profile.

Prediction of morbidity and mortality after early cholecystectomy for acute calculous cholecystitis: results of the S.P.Ri.M.A.C.C. study.

BACKGROUND: Less invasive alternatives than early cholecystectomy (EC) for acute calculous cholecystitis (ACC) treatment have been spreading in recent years. We still lack a reliable tool to select high-risk patients who could benefit from these alternatives. Our study aimed to prospectively validate the Chole-risk score in predicting postoperative complications in patients undergoing EC for ACC compared with other preoperative risk prediction models. METHOD: The S.P.Ri.M.A.C.C. study is a World Society of Emergency Surgery prospective multicenter observational study. From 1st September 2021 to 1st September 2022, 1253 consecutive patients admitted in 79 centers were included. The inclusion criteria were a diagnosis of ACC and to be a candidate for EC. A Cochran-Armitage test of the trend was run to determine whether a linear correlation existed between the Chole-risk score and a complicated postoperative course. To assess the accuracy of the analyzed prediction models-POSSUM Physiological Score (PS), modified Frailty Index, Charlson Comorbidity Index, American Society of Anesthesiologist score (ASA), APACHE II score, and ACC severity grade-receiver operating characteristic (ROC) curves were generated. The area under the ROC curve (AUC) was used to compare the diagnostic abilities. RESULTS: A 30-day major morbidity of 6.6% and 30-day mortality of 1.1% were found. Chole-risk was validated, but POSSUM PS was the best risk prediction model for a complicated course after EC for ACC (in-hospital mortality: AUC 0.94, p < 0.001; 30-day mortality: AUC 0.94, p < 0.001; in-hospital major morbidity: AUC 0.73, p < 0.001; 30-day major morbidity: AUC 0.70, p < 0.001). POSSUM PS with a cutoff of 25 (defined in our study as a 'Chole-POSSUM' score) was then validated in a separate cohort of patients. It showed a 100% sensitivity and a 100% negative predictive value for mortality and a 96-97% negative predictive value for major complications. CONCLUSIONS: The Chole-risk score was externally validated, but the CHOLE-POSSUM stands as a more accurate prediction model. CHOLE-POSSUM is a reliable tool to stratify patients with ACC into a low-risk group that may represent a safe EC candidate, and a high-risk group, where new minimally invasive endoscopic techniques may find the most useful field of action. TRIAL REGISTRATION: ClinicalTrial.gov NCT04995380.